Preparation of bicyclical lactams

ABSTRACT

1,8-Diaza-9,10-dialkyl-bicyclo-(4,4,0)-decane-(2,7)-diones are prepared by reacting a dicyanoethylated ketone, such as 2,2-di (beta-cyanoethyl)-butanone-3 in the presence of an inert solvent, such as methyl alcohol, and a basic catalyst at a temperature of about 20* to about 200* C.

United States Patent 1 Cherubim et al.

[ 1 Sept. 18, 1973 1 PREPARATION OF BICYCLICAL LACTAMS [75] Inventors:Martin Cherubim, Rheinkamp-Eick; Faisal Abodagga, Rheinkamp-Utfort, bothof Germany [73] Assignee: Deutsche Texaco Aktiengesellschaft, Munich,Germany [22] Filed: Aug. 28, 1972 [21] Appl. No.: 284,191

[30] Foreign Application Priority Data FOREIGN PATENTS OR APPLICATIONS1,110,895 4/1968 Great Britain 260/293.55

OTHER PUBLICATIONS Badger, J. Chem. Soc. 1949, 1141-1144.

Primary Examiner-Henry R. Jiles Assistant Examiner-G. Thomas ToddAtt0rney-Thomas H. Whaley et a1.

[57] ABSTRACT 1,8-Diaza 9,10-dialkyl-bicyclo-(4,4.,O)-decane-(2,7)-diones are prepared by reacting a dicyanoethylated ketone, such as2,2-di (beta-cyanoethyl)-butanone-3 in the presence of an inert solvent,such as methyl alcohol, and a basic catalyst at a temperature of about20 to about 200 C.

9 Claims, No Drawings This invention relates to bicyclical lactams andto a process for their preparation. More particularly this inventionrelates to l,8-diaza-9,lO-dialkyI-bicyclo- (4,4,0)- decane-(2,7-diones.These bicyclical lactams are hereinafter called Dibidon."

A known method of producing lactams is to heat amino acids at arelatively high temperature. The lactams obtained in moderate yields bythis method are, however, susceptible to be split up again to the aminoacids when the reaction is conducted in the presence of acids andalkalies. Surprisingly, it has been found that bicyclical lactams of theDibidon type may be obtained in relatively good yields by reactingdicyanoethylated ketones in alkaline solutions.

With the present invention l,8-diaza-9,l-dialkylbicyclo-(4,4,0)-decane-(2,7 )-diones of the general formula:

are prepared by reacting a dicyanoethylated ketone of the generalformula:

CHr-CHz-CN RA- R| H CHr-CN in which R, and R are independently selectedalkyl groups having from 1 to carbon atoms in the presence of a solventand a basic catalyst at a temperature of be tween about and 200 C.

The formation of lactams of the.Dibidon type described above issurprising inasmuch as cyclization under these conditions has heretoforenot been observed. Bicyclical compounds of the above-mentioned formulahave not been produced thus far.

Ketones useful as starting materials in the process of this inventioninclude, for example:

2,2-di (beta-cyanoethyl)-butanone-3,

2,2-di (beta-cyanoethyl)-pentanone-3,

2,2-di (beta-cyanoethyl)-4-rnethyl-pentanone-3 2,2-di(beta-cyanoethyl)-5-methyl-hexanone'3,

3 ,3 -di (beta-cyanoethyl )-octanone-4,

3,3-di (beta-cyanoe thyl)-2-methyl-octanone-4,

4,4-di (beta-cyanoethyl)-2,6-dimethyl-octanone-5 and 4,4-di(beta-cyanoethyl)-decanone-5.

An especially valuable group of ketones are those of the above-definedformula wherein R and R are independently selected alkyl groups havingfrom 1 to 3 carbon atoms as exemplified by methyl, ethyl, isopropyl,etc.

A wide variety of inert solvents may be employed in conducting thereaction. Advantageously, polar solvents such as primary, secondary ortertiary alcohols are used. For example, methanol, ethanol, isopropanolor tert.-butanol may be utilized as solvents. The amount of the solventused may be varied widely although generally from about 100 to about1500 and,

2 preferably, from about to about 1000 grams of the inert solvent permole of the dicyanoethylated ketone charged to the reactor is employed.Preferably, the reaction is conducted under reflux conditions in boilingalcohol with temperature ranging from about 60 to about C.

Suitable basic catalysts include alkali metal hydroxides, alkaline earthhydroxides, alkali metal alcoholates, or alkaline earth alcoholates,e.g., sodium hydroxide, potassium hydroxide, magnesium hydroxide, sodiumisopropylate, sodium tert.-butylate, etc. Usually from about 001 toabout 0.5 mole of the basic catalyst per mole of dicyanoethylated ketoneis used.

Recovery of the bicyclical lactams from the reaction mixture can beaccomplished in a number of ways. For example, the lactam product may beremoved from the reaction mixture by extraction with a suitable solventsuch as chloroform, the extract dried over sodium sulfate and theproduct recovered by evaporation of the solvent.

The composition and structure of the compounds of this invention havebeen ascertained by carbonhydrogen-nitrogen elemental analysis, proof offunctional groups, preparation of derivatives UV, IR, NMR, and massspectrophotometry as well as by detennination of the molecular weight.

Saponification of 1,8-diaza-9, l O-dimethylbicyclo-(4,4,0)-decane-(2,7)-dione, i.e.,dimethyl-Dibidon, produced according tothe process of this invention in aqueous KOH (potassium hydroxidesolution) leads to the corresponding dicarboxylic acid:

1 ,8-diaza-9,10-dimethyl-bicyclo-(4,4,0)-decane- (2,7)-dione issaponified by appropriately mixing 50 grams of this compoundcorresponding to 0.138 mole, with 50 grams of potassium hydroxide and500 grams of water and heating the mixture at reflux for 13 hours. Then,the reaction mixture is mixed with 200 ml of water and acidified withconcentrated hydrochloric acid up to a pH value of unity, followed byextraction with ethyl acetate. The extracts are dried over sodiumsulfate, filtered and concentrated. The residue is recrystallized fromethyl acetate. Yield:55.5 grams (=85.6 percent of theory) of4-methyl-4-acetoxy pimelic acid having a melting point of C. Thesecompounds are efficient bactericides. Because of their structure theymay also be used as bacteriostatics or they may be applied in otherfields of pharmaceutics. The use of the Dibidon type bicyclical dionesof this invention in dissolved form or in combination with liquidsubstances as selective solvents is, another interesting aspect. Thecompounds produced according to the invention may be'used asintermediate products for organic syntheses, as raw material forplastics, e.g., in the production of polyamides, epoxide resins orformaldehyde crosslinked resins. Their derivatives, obtained bymethylolation, can be used in textile finishing.

The compounds may be reacted with alcohols in an acidic or alkalinemedium to form esters or polyesters. If they are reacted withbifunctional amines, polyamides result. The so obtained products may beutilized as raw materials for plastics and also, for example, as epoxidehardeners.

The invention isfurther illustrated by the following examples which areto be considered not limitative:

EXAMPLE 1;

pH value of 5. The solution is then extracted several 10 times withchloroform and the extraction mixture dried with sodium sulfate. Thesolvent is removed in a rotary evaporator. 47 grams ofl,8-diaza-9,l-dimethylbicyclo-( 4,4,0)-decane-(2,7 )-dione, acrystalline product recrystallized from ethanol and having a melting 1point of 237 C, are obtained. Yield of the pure product: approximately80 percent of theory.

CHN analysis C H N molar weight Calculated 6L2 8.22 14.28 196 Found 61.18.0 14.4 191 EXAMPLE 2:

l ,8-diaza-9, l O-dimethyl-bicyclo-(4,4,0 )-decane- (2,7)-dione 100grams of 2,2-di( beta-cyanoethyl)-butanone-3, corresponding to about0.56 mole, are heated at reflux for 28 hours with 500 ml oftert.-butanol and 50 ml of a 10 percent potassium hydroxide solution.After cooling, 200 ml of water are added and the mixture is neutralizedwith diluted hydrochloric acid. The product is extracted several timeswith chloroform, the extract is dried with sodium sulfate andsubsequently distilled in a rotary evaporator. The obtained raw productis recrystallized from ethanol. Yield: 90 grams, of 1,8- diaza-9, l0-dimethyl-bicyclo-(4,4,0 )-decane-( 2,7 dione corresponding to 82percent of theoretical yield. Melting point: 237 to 238 C.

CHN ANALYSIS mula:

R1 i NA which comprises reacting a dicyanoethylated ketone of theformula:

wherein R and R are independently selected alkyl groups having from 1 to5 carbon atoms, in the presence of an inert solvent and a basic catalystat a tem- 5 perature of between about 20 and 200 C.

2. The process of claim 1 wherein the said basic catalyst is selectedfrom the group consisting of alkali metal hydroxides, alkaline earthhydroxides, alkali metal a1- coholates and alkaline earth alcoholates.

3. The process of claim 2 wherein from about 0.01 to about 0.5 mole ofthe said basic catalyst is employed per mole of dicyanoethylated ketone.

4. The process of claim 1 wherein the said dicyanoethylated ketone isreacted with about 200 to about 1000 grams of solvent per mole ofdicyanoethylated ketone.

5. The process of claim 1 wherein the said solvent is selected from thegroup consisting of primary, secondary and tertiary alcohols.

6. The process according to claim 1 wherein the said solvent is selectedfrom the group consisting of methanol, ethanol, isopropanol andtert.-butanol.

7. The process of claim 1 wherein the reaction is conducted at atemperature of between 60 and 120 C.

8. A compound of the formula:

' (2,7 )-dione.

2. The process of claim 1 wherein the said basic catalyst is selectedfrom the group consisting of alkali metal hydroxides, alkaline earthhydroxides, alkali metal alcoholates and alkaline earth alcoholates. 3.The process of claim 2 wherein from about 0.01 to about 0.5 mole of thesaid basic catalyst is employed per mole of dicyanoethylated ketone. 4.The process of claim 1 wherein the said dicyanoethylated ketone isreacted with about 200 to about 1000 grams of solvent per mole ofdicyanoethylated ketone.
 5. The process of claim 1 wherein the saidsolvent is selected from the group consisting of primary, secondary andtertiary alcohols.
 6. The process according to claim 1 wherein the saidsolvent is selected from the group consisting of methanol, ethanol,isopropanol and tert.-butanol.
 7. The process of claim 1 wherein thereaction is conducted at a temperature of between 60* and 120* C.
 8. Acompound of the formula: 9.1,8-diaza-9,10-dimethyl-bicyclo-(4,4,0)-decane-(2,7)-dione.